Type 2 Diabetes Mellitus Flashcards
What risk factors influence the occurrence of T2DM?
Genetics, obesity and lack of exercise can all lead to increased risk of T2DM.
What insulin mechanisms are associated with T2DM?
Insulin resistance and impared insulin secretion is associated with T2DM.
What are the events that cause Insulin resistance and impaired secretion?
Diet elevates insulin levels.
These bombarded the corresponding receptors leading to unresponsive tissue due to downregulation and impared signalling.
Due to Insulin not being able to exert effects blood glucose increases stimulating release of more Insulin depleting pancreatic Beta cells causing impaired Insulin secretion and hyperinsulinaemia.
What is meant by the term impaired glucose tolerance?
IGT is a pre-diabetic state of hyperglycaemia associated with insulin resistance.
How is impaired glucose tolerance detected?
IGT is detected via the use of testing blood levels 2 hour after glucose challenge.
What non pharmacological advice can be given in the management of T2DM?
Change diet, Weight loss, Increase physical activity
What are the broad goals of pharmacological treatment that can be given in the management of T2DM?
Increasing insulin secretion
Carbohydrate metabolism antagonist
Insulin supplements
Metformin is a class of hypoglycaemic drugs. How does it work?
Metformin (Biguanides) reduces glucose production, increases glucose uptake, reduces carbohydrate absorption and reduces VLDL/LDL levels.
How are sulphonylureas used to treat T2DM?
Sulphonylureas such as Gilpizide and Gliclazide work by increasing insulin secretion which reduces blood glucose.
They block outflux of K+ ions, so it accumulates causing calcium entry and thus exocytosis of insulin granules
Only effective when there are functional b cells available
How do sulphonylureas preform their mechanism of action?
They bind to SUR1 receptors on potassium channels causing depolarisation which then triggers an infux of calcium ions causing a secretion of insulin from granules.
How are Thiazolidinediones used to result in hypoglycaemia and what are they not used as much now?
Pioglitazone reduces glucose output and increases its uptake, it also reduces insulin required to regulate blood by 30% but is not used due to incidence of heart failure.
How do thiazolidinediones exert their effects and what overall changes occur as a result?
They form heterodimers which bind to PPRE in the enhancer regions of the target genes causing increase uptake of fatty acids and glucose into cells.
How are glucoside inhibitors used in the treatment of T2DM?
They inhibit the intestinal hormone glucosidase which leads to delays in carb absorption and reducing blood glucose increases after eating.
What do gliptins inhibit the breakdown of and what does this then cause?
They inhibit DDP4 which prevents the breakdown of incretins which decreases blood glucose.
How is the synthetic peptide incretin mimetics used for the treatment of T2DM?
This peptide incretin stimulates insulin secretion, inhibiting pancreatic glucagon secretion aswell as slowing rate of digested food absorption.
